Trials / Recruiting

RecruitingNCT01371630

Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Patients With Acute Lymphoblastic Leukemia

Phase I/II Study of the Combination of Inotuzumab Ozogamycin (CMC-544) With Low-Intensity Chemotherapy in Patients With Acute Lymphoblastic Leukemia (ALL)

Status: Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 276 (estimated)

Sponsor: M.D. Anderson Cancer Center · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of inotuzumab ozogamicin and to see how well it works when given together with combination chemotherapy in treating patients with acute lymphoblastic leukemia. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called N-acetyl-gamma-calicheamicin dimethyl hydrazide (CalichDMH). Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers CalichDMH to kill them. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving inotuzumab ozogamicin together with combination chemotherapy may be a better treatment for acute lymphoblastic leukemia.

Detailed description

PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin (inotuzumab ozogamycin) in combination with low-intensity chemotherapy in elderly patients (age 60 or older) with acute lymphoblastic leukemia (ALL). (Phase I) II. Evaluate the efficacy of inotuzumab ozogamycin in combination with low-intensity chemotherapy in elderly and unfit to receive intensive therapy patients with ALL. (Phase II) III. To evaluate the side effects of the treatment. (Phase II) IV. Evaluate the regimen efficacy in refractory-relapsed ALL. (Phase II) EXPLORATORY OBJECTIVES: I. To identify genomic alterations in adult ALL predictive for response and long-term outcomes with the combination of hyper-CVD (cyclophosphamide, dexamethasone, methotrexate, and cytarabine) + inotuzumab + blinatumomab. II. To evaluate the impact of next generation sequencing (NGS)-based minimal residual disease (MRD) assay on outcomes and to compare with standard flow cytometry MRD assays. OUTLINE: This is a phase I, dose-escalation study of inotuzumab ozogamicin followed by a phase II study. Patients are assigned to 1 of 3 arms. ARM I (UNTREATED): CYCLES 1, 3, 7, AND 9: Patients receive cyclophosphamide intravenously (IV) over approximately 3 hours twice daily (BID) on days 1-3; vincristine IV over 30 minutes on days 1 and 8; dexamethasone IV or orally (PO) on days 1-4 and 11-14; inotuzumab ozogamicin IV over approximately 1 hour on day 3 of cycle 1 and day 2 or 3 of cycle 3; methotrexate intrathecally (IT) on day 2 of cycles 1 and 3; and cytarabine IT on day 8 of cycles 1 and 3. Patients may also receive rituximab IV on days 1 and 8 of cycles 1 and 3. Cycles alternate every 3-4 weeks in the absence of disease progression or unacceptable toxicity. CYCLES 2, 4, 8, AND 10: Patients receive methotrexate IV over approximately 2 hours and then continuously over approximately 22 hours on day 1; cytarabine IV over approximately 3 hours BID on days 2-3; inotuzumab ozogamicin IV over approximately 1 hour on day 2 or 3 of cycles 2 and 4; cytarabine IT on day 5 of cycles 2 and 4; and methotrexate IT on day 8 of cycles 2 and 4. Patients may also receive rituximab IV on days 1 and 8 of cycles 2 and 4. Cycles alternate every 3-4 weeks in the absence of disease progression or unacceptable toxicity. CYCLES 5-8: Patients receive blinatumomab as a continuous intravenous infusion (CIVI) on days 1-29. Patients also receive dexamethasone IV over 15-30 minutes on day 1 and 3 of cycle 5 and then day 1 of cycles 6-8. Treatment repeats every 42 days for 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive mercaptopurine PO BID and methotrexate PO once weekly for 3 years. Patients also receive vincristine IV over 30 minutes once monthly and prednisone PO daily five times a month for 1 year. Patients receive blinatumomab CIVI on days 1-28 of cycles 4, 8, 12, and 16. Cycles repeat every 42 days for 3 years in the absence of disease progression or unacceptable toxicity. ARM II (RELAPSED/REFRACTORY): CYCLES 1, 3, AND 5: Patients receive cyclophosphamide IV over approximately 3 hours BID on days 1-3; vincristine IV over 30 minutes on day 1; rituximab IV over 2-6 hours on days 1 and 8 of cycles 1 and 3; dexamethasone IV or PO on days 1-4; inotuzumab ozogamicin IV over 1 hour on days 2 and 8; methotrexate IT on day 2 of cycles 1 and 3; cytarabine IT on day 8 of cycles 1 and 3; and blinatumomab CIVI on days 4-21. Cycles alternate every 4 weeks in the absence of disease progression or unacceptable toxicity. CYCLES 2, 4, AND 6: Patients receive methotrexate IV over 24 hours on day 1; cytarabine IV over approximately 3 hours BID on days 2-3; rituximab IV over 2-6 hours on days 1 and 8 of cycles 2 and 4; inotuzumab ozogamicin IV over 1 hour on days 2 and 8 of cycles 2 and 4; cytarabine IT on day 2 of cycles 2 and 4, methotrexate IT on day 8 of cycles 2 and 4; and blinatumomab CIVI on days 4-21. Cycles alternate every 4 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive mercaptopurine PO BID and methotrexate PO once weekly for 3 years. Patients also receive vincristine IV over 30 minutes once monthly and prednisone PO daily five times a month for 1 year. Patients receive blinatumomab CIVI on days 1-28 of cycles 4, 8, 12, and 16. Cycles repeat every 42 days for 3 years in the absence of disease progression or unacceptable toxicity. ARM III (70 YEARS AND OLDER): INDUCTION CYCLE (CYCLE 1): Patients receive dexamethasone IV or PO on days 1-4; vincristine IV over 30 minutes on day 1; inotuzumab ozogamicin IV over 1 hour on days 1 and 8 of cycle 1; blinatumomab CIVI on days 15-28. Patients may also receive rituximab IV on days 2 and 9. INTRATHECAL PROPHYLAXIS: Patients receive methotrexate IT alternating with cytarabine IT on days 2 and 8 of cycles 1 and 3, and cytarabine IT alternating with methotrexate IT on days 2 and 8 of cycles 2 and 4. Treatment repeats every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION (CYCLES 2-5): Patients receive blinatumomab CIVI on days 1-28; inotuzumab ozogamicin IV over 1 hour on days 1 and 8 of cycles 2-4. Patients may also receive rituximab IV on days 2 and 9 of cycles 2-4. Treatment repeats every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and every 4 months.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	Blinatumomab	Given CIVI
DRUG	Cyclophosphamide	Given IV
DRUG	Cytarabine	Given IT and IV
DRUG	Dexamethasone	Given IV or PO
BIOLOGICAL	Inotuzumab Ozogamicin	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Mercaptopurine	Given PO
DRUG	Methotrexate	Given IT, IV, and PO
DRUG	Prednisone	Given PO
BIOLOGICAL	Rituximab	Given IV
DRUG	Vincristine	Given IV

Timeline

Start date: 2011-08-26
Primary completion: 2027-12-25
Completion: 2027-12-25
First posted: 2011-06-13
Last updated: 2025-12-18

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT01371630. Inclusion in this directory is not an endorsement.